Abstract

Objective

To compare the short-term effectiveness of once-daily with twice-daily inhaled beclomethasone
dipropionate in adults with moderate asthma.

Design

14-week, randomized, double-blind, crossover trial.

Setting

A Canadian tertiary care asthma clinic.

Patients

42 patients (mean age 39 y, 55% men) with moderate asthma using the American Thoracic
Society definition confirmed by spirometric criteria. Inclusion criteria were a need
for at least 1000 µg of beclomethasone or 800 µg of budesonide for optimal control
of asthma, an FEV1 > 60% of predicted while being treated with inhaled steroids, no increase in respiratory
symptoms or medication in the previous 4 weeks, and no symptomatic exposure to allergens
or a respiratory infection in the previous month.

Intervention

After a 2-week evaluation period, patients were allocated to each of three, 4-week
beclomethasone regimens, the order being determined by random allocation: regimen
A, morning and bedtime dose of 500 µg; regimen B, 1000 µg in the late afternoon; and
regimen C, 1000 µg at bedtime. Blinding was maintained using 4 metered-dose inhalers
daily. Patients used albuterol inhalers as needed for symptom control. Follow-up was
88%.

Main outcome measures

Main results

4 patients withdrew because of exacerbation: 1 during baseline, 1 during the twice-daily
regimen, and 2 during the afternoon single-dose regimen. The values of the major outcomes
for regimens A, B, and C were as follows: albuterol use, 3.3, 3.1, and 3.3 puffs/d;
mean daytime respiratory symptoms, 0.3, 0.22, and 0.28; FEV1, 85%, 84%, and 84% predicted; and peak expiratory flow rates (morning/evening), 451/454,
441/459, and 447/452 L/min, respectively. None of the differences approached conventional
levels of statistical significance. Side effects were minimal, and cortisol levels
and response to adrenocorticotropic hormone remained normal throughout the study period.

Conclusion

Single- and twice-daily administration of beclomethasone were equally effective for
short-term control of symptoms of moderate asthma.

Commentary

Inhaled corticosteroids offer the benefits of oral corticosteroids with a more favorable
side effect profile (1-3). 3 aerosol corticosteroids are currently available in the
United States: beclomethasone, flunisolide, and triamcinolone. All are effective for
asthma management; however, much of the published data on efficacy and safety are
from studies of beclomethasone. Because the primary therapeutic aim in asthma management
is to decrease airway hyper-responsiveness, greater use of inhaled corticosteroids,
which are very effective in achieving this goal, has been encouraged (1). Adherence to a regimen stipulating regular medication use on a 3-to-4 times/d schedule
is poor (2). Consequently, studies indicating that an inhaled corticosteroid was equally effective
when used once daily are of considerable importance because these regimens are likely
to promote higher rates of adherence.

The study by Gagnon and colleagues shows that a similar level of asthma control was
achieved with once-daily compared with twice-daily administration of inhaled corticosteroid.
It is important to note, however, that patients received relatively high-dose (1000
µg/d) beclomethasone regimens (3, 4). Beclomethasone inhalers containing 250 µg per puff have been used in the United
Kingdom since 1974 (4). Beclomethasone inhalers currently available in the United States, however, deliver
only 42 µg per puff; hence, 24 puffs of beclomethasone would be required to achieve
drug delivery equivalent to the regimen used in this investigation.

Persons with stable, moderate asthma were studied for 14 weeks. Therefore, these findings
cannot be extended to persons with severe or moderate-to-severe asthma, or persons
with unstable asthma. The latter point is important in view of the capricious nature
of asthma and the reduced efficacy of less frequent inhaled corticosteroid dosing
in the setting of asthmatic relapse (2). Further investigation is required before a once-daily dosing schedule for long-term
inhaled corticosteroid use can be recommended.

David Lang, MDHahnemann UniversityPhiladelphia, Pennsylvania, USA

References

1. National Heart, Lung, and Blood Institute. Guidelines for the diagnosis and management of asthma. Bethesda MD: U.S. Department
of Health and Human Services, 1991. Publication No. 91-3042.